Significance The cellular events leading to birth defects following exposure to an environmental agent are largely unknown. However, recent studies in laboratory species have advanced our understanding of the molecular mechanisms of a known human teratogen, 13-cis retinoic acid (cRA, isotretinoin, Accutane). Objectives The present study was carried out to study the molecular/cellular consequences of embryonic exposure to cRA in the cynomolgus monkey. We have previously demonstrated that the human cRA syndrome can be modeled in this species due to striking similarities in malformations, teratogenic dose, and sensitive period during early pregnancy. Results Immunohistochemistry using antibodies to neurofilaments and cellular retinoic acid binding protein-1 as well as Hox-B1, Krox-20 and Pax-2 gene products showed hypoplasia, abnormal, or delayed development of the hindbrain, cranial neural crest cells, and otocyst. Scanning electron microscopy indicated hypoplasia and/or abnormal development of the first and second pharyngeal arches (the precursors of the face). Coordinated development of all these embryonic structures is necessary for morphogenesis of the brain, ears, and face. Thus, the current observations are consistent with the malformations observed in cynomolgus fetuses exposed to the same regimen of cRA during early pregnancy. These include under development and/or duplication of the ear (external, middle, internal), face and cerebellum as well as cerebellar hypoplasia/aplasia. Future Directions Use of additional molecular markers, including riboprobes, to study alterations in gene expression patterns in the developing brain and craniofacial region after cRA exposure. KEYWORDS retinoids, birth defects, molecular mechanisms